Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2026 Mar 7.
doi: 10.1002/mus.70212. Online ahead of print.

Integrating Serum Neurofilament Light Chain Into Amyotrophic Lateral Sclerosis Diagnostic Criteria

Sean E Smith  1 , Timothy M Miller  1 , Andrew Atkinson  2 , Alan Pestronk  1 , Robert C Bucelli  1
Affiliations

Integrating Serum Neurofilament Light Chain Into Amyotrophic Lateral Sclerosis Diagnostic Criteria

Sean E Smith et al. Muscle Nerve. .

Abstract

Introduction/aims: Serum neurofilament light chain (NfL) is a promising diagnostic biomarker for differentiating amyotrophic lateral sclerosis (ALS) from clinical mimics. This study assessed the utility of integrating serum NfL into current diagnostic criteria to enhance diagnostic certainty in patients with a provisional ALS diagnosis who were confirmed as having ALS at follow-up.

Methods: We conducted a single-center, retrospective study of consecutive patients with a provisional ALS diagnosis at their initial visit at the WashU Medicine ALS Center. All underwent electrodiagnostic testing and serum NfL measurement via SIMOA using an HD-X analyzer (Quanterix). Elevated serum NfL was defined with a cutoff of 38 pg/mL.

Results: The study included 43 patients with a provisional ALS diagnosis (29 men [67.4%]; median age, 63 years [range, 36-80 years]). At follow-up, 27/43 (62.8%) patients progressed to definite ALS. Serum NfL was elevated in 34/43 (79.1%) of the total cohort and 24/27 (88.9%) of those who progressed to definite ALS. Integrating serum NfL with Gold Coast Criteria (GCC) was associated with a tenfold increase in the odds of identifying patients likely to progress to definite ALS (OR 10 [1.39, 71.87], p = 0.02).

Discussion: Our results suggest that serum NfL is a robust complement to current ALS diagnostic criteria and shows potential to improve early identification and diagnostic certainty of patients likely to progress to definite ALS. Integrating serum NfL with GCC provided the strongest predictive model. These findings warrant larger multicenter, prospective studies to confirm results.

Keywords: amyotrophic lateral sclerosis; biomarker; diagnostic criteria; disease progression; neurofilament.

PubMed Disclaimer

References

    1. E. Feneberg, P. Oeckl, P. Steinacker, et al., “Multicenter Evaluation of Neurofilaments in Early Symptom Onset Amyotrophic Lateral Sclerosis,” Neurology 90, no. 1 (2018): e22–e30.
    1. D. W. Li, H. Ren, A. Jeromin, et al., “Diagnostic Performance of Neurofilaments in Chinese Patients With Amyotrophic Lateral Sclerosis: A Prospective Study,” Frontiers in Neurology 9 (2018): 726.
    1. S. Halbgebauer, P. Steinacker, F. Verde, et al., “Comparison of CSF and Serum Neurofilament Light and Heavy Chain as Differential Diagnostic Biomarkers for ALS,” Journal of Neurology, Neurosurgery, and Psychiatry 93, no. 1 (2022): 68–74.
    1. M. Benatar, J. Wuu, and M. R. Turner, “Neurofilament Light Chain in Drug Development for Amyotrophic Lateral Sclerosis: A Critical Appraisal,” Brain 146, no. 7 (2023): 2711–2716.
    1. B. R. Brooks, R. G. Miller, M. Swash, T. L. Munsat, and World Federation of Neurology Research Group on Motor Neuron Diseases, “El Escorial Revisited: Revised Criteria for the Diagnosis of Amyotrophic Lateral Sclerosis,” Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 1, no. 5 (2000): 293–299.

LinkOut - more resources